Blood borne viral infections are extremely difficult to treat or cure once a patient is infected with the virus. Blood borne viruses can completely inundate the patient (i.e., the "host") and defeat the patient's immune system, which almost certainly leads to death of the patient. Examples of viral infections affecting humans include polio, measles, chicken pox, small pox, mumps, Ebola, the common cold and the human immunodeficiency virus ("HIV"). In addition, animals are affected by other viral infections. For example, cattle can be infected by foot-and-mouth disease, dogs can be infected by distemper, cats can be infected by panleukopenia and feline immunodeficiency virus, and hogs can be infected by cholera.
The HIV virus has become a leading cause of death among humans. The prior art has not provided an effective antiviral agent which can effectively kill the HIV virus, thereby leading to either a cure or an effective treatment for infected patients.
The mechanisms of viral infections and specifically the HIV virus will now be discussed so as to provide background into how the present invention acts to kill viruses that have infected a patient. A virus is not an independent living organism. Outside of living cells, for example in body fluids, some viruses can remain dormant. They do not reproduce, metabolize, grow or assimilate food. For a virus to live and reproduce, it needs a host cell. Thus, until a virus finds a host cell, it it may remain dormant in body fluids. During this dormancy period, the virus may come in contact with a suitable host.
Viruses have many different shapes and sizes. For example, the individual virus or virions can be spherical, rod-shaped, or can have a many headed configuration. Virions range in size from approximately 0.02 microns to approximately 0.25 microns. The smallest living bacterium is approximately 0.4 microns. Virions are generally comprised of a viral core which is made up of nucleic acids which carry the viral genes and a capsis of fatty materials and proteins which surrounds the core. In some cases, viral proteins are associated with the nucleic acid in the viral core. This capsis may be surrounded by an additional lipoprotein envelope. The virus attacks a cell by causing at least its nucleic acid to enter the cell. The virus then takes over the cell's metabolic machinery and uses it to make many of copies of itself, thus producing many new virions. In the case of the HIV virus, the virions are released from the cell by lysing (i.e., the cell bursts), which destroys the cell. Many of the virions, however, are able to go on to infect other cells, which are eventually killed.
Humans and other animals have developed natural defenses to viruses. One of the body's first reactions to infection by a virus is a fever. Fever is often the only response necessary since elevated temperatures can deactivate many viruses. Other viruses cause cells to secrete the protein interferon. Interferon can inhibit the production of virions in uninfected cells. Another reaction to infection by a virus is the production of antibodies and activation of other parts of the body's immune system, which can inactivate the virus. Different viruses result in the production of different antibodies.
Part of the immune response of humans and other animals to viral infection is the production of T-lymphocytes and B-lymphocytes. T-lymphocytes and B-lymphocytes are classes of white blood cells that fight infection in a manner specific to the infecting agent. "B-cells" produce antibodies while "T-cells" have receptors on their surface that mate with the antigen of an invading agent. This mating prevents the invader from infecting other cells until that invading agent can be removed from the bloodstream by the kidneys. More than ten million different T-cell receptor patterns are known to exist. Once a specific T-cell has been produced to fight a specific agent, that T-cell continues to reproduce so that it is present at the time of the next infection by the agent it was created to fight. Approximately two-thousand T-cells can be produced by the body per second in a healthy individual.
The HIV virus is extremely deadly because it attacks these T-cells, eventually producing so many virions that attack the T-cells that the body cannot make T-cells fast enough to replace those destroyed by the HIV virus. The specific T-cell targeted by the HIV virus is the T4 helper lymphocyte. T4 cells are extremely important to the immune defense system of a human. T4 cells control the body processes which produce immune responses to infections. If a T4 cell determines that a response is necessary, it instructs the body's immune system to release T8 cytotoxic lymphocytes and antibodies.
When an HIV virion finds a T4 cell, it is believed that it attempts to penetrate the cell wall to gain access to the T4 cell's nucleus. Many believe that when the HIV virion contacts a T4 cell, the glycoproteins Gp120 and Gp41 on the exterior of the HIV virion attach the virion to CD4 proteins protruding from the T4 cell's surface. After attachment, it is thought that the HIV virus fuses with the T4 cell and injects capsid protein P24 with the genomic ribonucleic acid ("RNA") of HIV and reverse transcriptase, RNaseH, and integrase into the cell. After the HIV virus is injected into the cell, the reverse transcriptase, RNaseH, and integrase manufacture HIV deoxyribonucleic acid ("DNA") out of the genomic RNA. After the HIV DNA is manufactured within the cell, the HIV DNA enters the cell's nucleus and splices itself into one of that cell's chromosomes. At this point, the T4 cell is infected with the HIV virus.
Once the T4 cell is infected with the HIV virus, the T4 cell begins to reproduce copies, i.e., virions, of the HIV virus. One infected T4 cell can produce approximately three hundred thousand to one million copies of the HIV virus per infected T4 cell. Eventually, the infected T4 cell lyses, which destroys the cell. The copies of the infecting HIV virus released from the destroyed T4 cell go on, however, to infect other T4 cells. Since an infected T4 cell produces copies of the HIV virus faster than humans can produce T4 cells, eventually the immune system of the infected person is overrun and is unable to fight off infection. This is because there are too few T4 cells left to create an immune response to invading agents. It is these infections which eventually lead to the death of a patient from the HIV virus. Furthermore, copies of the HIV virus are created faster than the antibody the body creates to fight it. Since the T4 cells are destroyed faster than they can be reproduced, the body will never be able to create enough HIV antibody to fight the virus.
The prior art teaches that infection by many viruses can be prevented by vaccination. Vaccination involves injecting an uninfected patient with a weakened or denatured virus. In response to the weakened or denatured virus, the body will create antibodies specific to that virus. With respect to the HIV virus, however, there is no known vaccine. Further, because the HIV virus mutates so rapidly, a vaccine may not be possible. The prior art does teach several drug therapies for a person infected with the HIV virus. Prior art drug therapies include Azidothymidine, known as AZT, Dideooxyinosine, known as ddI, and Zalcitabine, known as ddc. Recently, a new class of drugs, for example Zidovudine, known as ZDV, and Saquinavir, ddc known as Invirase.TM., have been used for treating HIV infected patients. ZDV and Saquinavir are members of a class of drugs known as protease inhibitors. AZT tends to slow the HIV virus' reproduction cycle in humans. This lengthens the amount of time that it takes for the HIV virus to completely destroy the immune system. ddI has results similar to AZT and tends to be used if AZT is too toxic for a particular patient. ddc is generally used in combination with AZT to treat advanced HIV infection. AZT, ddI, and ddc are nucleotide analogues which make it difficult for the HIV virus to replicate by interfering with the reverse transcriptase. ZDV and other protease inhibitors are anti-retroviral agents that interfere with the replication machinery of HIV, resulting in non-infectious. Because the HIV virus mutates so rapidly, however, the virus within a patient eventually becomes immune to protease inhibitors.
Further, prior art methods have developed whereby the patient takes several different medications at the same time. These drug combinations have become known in the art as "cocktails." Cocktails of these drugs are proving somewhat effective at delaying the destruction of the immune system by the HIV virus. However, the HIV virus eventually does overrun the immune system in patients undergoing this therapy for the reasons discussed above. Furthermore, such treatment is extremely disruptive to the patient, as often the patient will be required to take thirty to forty pills at many different times during the day. The long-term results of these three-drug combinations are not yet known. Furthermore, the cost of the three-drug combination is extremely high and is therefore beyond the reach of many infected individuals. Finally, the three-drug treatments are not well tolerated by some patients.
Thus, there has been a long felt need for a treatment of subjects infected with blood-borne pathogens, such as the HIV virus, which destroys the pathogen.